The goal of this proposal is to study the cellular/molecular mechanisms by which mechanical stress inhibits cardiomyocyte apoptosis. Heart failure is a leading cause of disability and death in the U.S. Although it has been recognized that apoptosis occurs in human failing hearts, the role of mechanical stress in cardiomyocyte apoptosis has not been clearly defined. In this fellowship proposal, I will test the overall hypothesis that mechanical strain inhibits cardiomyocyte apoptosis through mechanically activated transcription factors, nuclear factor-Kappa B (NF-kappaB) and signal transducer and activator o transcription 3 (STAT3). To test this hypothesis, three specific aims will be pursued. Aim 1 : To determine whether mechanically activated NF-kappaB and STAT3 inhibit apoptosis of cardiac myocytes. Aim 2: To explore whether mechanically generated reactive oxygen species (ROS) activate NF-kappaB and STAT3 in cardiomyocytes. Aim 3: To assess whether mechanically activated NF-kappaB and STAT3 induce the expression of Bcl-xL, an anti-apoptotic member of the Bcl-2 family, in cardiomyocytes.